Although NMO CSF rAbs have been shown to bind to AQP4-expressing cells or CNS astrocytes and mediate target destruction by in vitro, ex vivo, and in vivo methods (3, 5, 20), the ability of autoantibodies against denatured or linear AQP4 epitopes to bind plasma membrane AQP4 and activate antibody effector function has not been tested. The gene discussed is AQP4; the disease is neuromyelitis optica.